Influence of chronic Naltrexone treatment on growth hormone and insulin secretion in obese subjects

Abstract

OBJECTIVE: Recent studies have demonstrated the restoration of a normal 24 h GH profile induced by a reduction of insulinaemia after weight loss, suggesting a reciprocal relationship between plasma insulin and GH concentrations. We aimed to clarify if an opiate-induced reduction in plasma insulin could affect GH secretion in obesity. DESIGN: We have studied the insulin response to an oral glucose tolerance test (OGTT) and the GH response to GHRH before and after prolonged treatment with Naltrexone (NTX). C-peptide, IGF-I, IGFBP-3 plasma levels and the IGF-I/IGFBP-3 molar ratio were also determined. SUBJECTS: Twelve obese women (aged 25–41 y; Body mass index (BMI): 31–39 kg/m²) and six lean normal women (aged 25–38; BMI: 19.8–23.1 kg/m²). MEASUREMENT: GH was determined by the IRMA method; insulin, C-peptide, IGF-I and IGFBP-3 were assayed by the RIA method. For molar comparison between IGF-I and IGFBP-3 we have considered 30.5 kDa the molar weight of IGFBP-3. Results are expressed as mean±s.e.m. RESULTS: We observed a significant decrease in basal concentration of both insulin (230.1±34.9 vs 133.2±16.9 pmol/L; P<0.005) and C-peptide (3.7±0.3 vs 2.4±0.1 µg/L; P<0.02). No modifications in the insulin secretory response to the OGTT were observed. A significant increase of the GHRH-induced GH peak response (7.7±1.4 vs 19.7±3.1 µg/L; P<0.01) and GH-AUC (533±151 vs 1415±339 µg/L/120 min; P<0.01) was found after NTX treatment. A negative correlation was found between basal insulin and GH peak values, both before (r=−0.641, P=0.027) and after NTX (r=−0.714, P=0.013). No modifications were found in IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio. Moreover, NTX affected neither the insulin response to OGTT or IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio in a group of six lean controls. Conversely, NTX significantly reduced the GH response to GHRH, when expressed as both peak and AUC values. CONCLUSIONS: The opiate antagonist significantly reduced basal insulin concentrations and augmented the GH response to GHRH in obese subjects. In the absence of modifications in IGF-I and IGFBP-3 plasma levels and their molar ratio, we propose that insulin may exert a negative feedback on GH secretion.